# Investigating the Role of Systemic Sex Hormones on Photoreceptor Degeneration

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $40,127

## Abstract

PROJECT SUMMARY
There is growing evidence that some diseases can be influenced by biological sex, where male or female patients
have worsened outcomes or faster disease progression. However, the molecular mechanisms underlying the
interaction of systemic sex hormones and disease are largely unknown. There is a critical need to understand
the molecular basis of how circulating sex hormones can impact disease progression. I have shown that a mouse
model of rhodopsin P23H Retinitis Pigmentosa (RP) presents as sexually dimorphic, where disease progression
is increased in females compared to males. RP is a group of devastating visual disorders that cause the death
of the photoreceptor neurons, leading to blindness. In addition to my findings of sexual dimorphism in retinal
disease progression in RP, I have discovered that this sex difference can be ameliorated by depletion of estrogen
and progesterone. Re-introduction of either of these sex hormones can worsen visual decline. The overall goal
of my work is to understand the mechanisms that influence photoreceptor cell death in RP. Specifically, this
proposal aims to determine how systemic sex hormones impact cell death and stress responses in the
rhodopsin (Rho) P23H form of RP. To do so, I will first employ targeted molecular biology techniques to
analyze the effect of circulating estrogen and progesterone on the unfolded protein response and caspase-
mediated cell death. By investigating these two pathways, I will describe how the hormones that are detrimental
to photoreceptor health in RP are affecting two of the central molecular mechanisms underlying this disease.
Next, I will investigate how these hormones are able to carry out their detrimental functions by defining the
hormone receptors that mediate this response through in vivo antagonist/ agonist studies. Furthermore, I will
determine the genetic control of the hormone signaling in the retina through RNA sequencing. Together, these
aims will inform how and what is being altered in the Rho P23H retina in response to hormone signaling.
Successful completion of this project will be vital for informing the clinical safety of hormonal medications for
patients with this form of RP, as well as discovering new pathways that can affect photoreceptor degeneration.
Furthermore, this work provides me the opportunity to advance my skills in the study of hormone signaling and
cellular stress and promotes my career goals of becoming an independent investigator.

## Key facts

- **NIH application ID:** 10997256
- **Project number:** 1F31EY036730-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Ashley Rowe
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,127
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997256

## Citation

> US National Institutes of Health, RePORTER application 10997256, Investigating the Role of Systemic Sex Hormones on Photoreceptor Degeneration (1F31EY036730-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10997256. Licensed CC0.

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